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World J Gastroenterol. Jul 21, 2014; 20(27): 8910-8920
Published online Jul 21, 2014. doi: 10.3748/wjg.v20.i27.8910
Possible biological and translational significance of mast cells density in colorectal cancer
Ilaria Marech, Michele Ammendola, Claudia Gadaleta, Nicola Zizzo, Caroline Oakley, Cosmo Damiano Gadaleta, Girolamo Ranieri
Ilaria Marech, Caroline Oakley, Cosmo Damiano Gadaleta, Girolamo Ranieri, Interventional Radiology Unit with Integrated Section of Translational Medical Oncology, National Cancer Research Centre Istituto Tumori “Giovanni Paolo II”, 70124 Bari, Italy
Michele Ammendola, Department of Clinical Surgery, University of Catanzaro “Magna Graecia” Medical School, 88100 Catanzaro, Italy
Claudia Gadaleta, Nicola Zizzo, Department of Pathology, Veterinary Medical School, University of Bari, Valenzano, 70010 Bari, Italy
Author contributions: Marech I, Gadaleta CD and Ranieri G ideated the manuscript and performed a critical review of the literature; Ammendola M, Gadaleta C and Zizzo N contributed to literature research and data analysis; Oakley C edited the manuscript; all authors wrote the manuscript.
Correspondence to: Girolamo Ranieri, MD, Interventional Radiology Unit with Integrated Section of Translational Medical Oncology, National Cancer Research Centre Istituto Tumori “Giovanni Paolo II”, Via Orazio Flacco 65, 70124 Bari, Italy. giroran@tiscalinet.it
Telephone: +39-80-5555561 Fax: +39-80-5555563
Received: September 23, 2013
Revised: January 24, 2014
Accepted: April 21, 2014
Published online: July 21, 2014
Processing time: 301 Days and 12 Hours
Abstract

Mast cells (MCs), located ubiquitously near blood vessels, are descended from CD34+ hematopoietic stem cells. Initially, although their role has been well defined in hypersensitivity reactions, the discovery of their sharing in both innate and adaptive immunity has allowed to redefine their crucial interplay on the regulatory function between inflammatory and tumor cells through the release of mediators granule-associated (mainly tryptase and vascular endothelial growth factor). In particular, in several animal and human malignancies it has been well demonstrated that activated c-Kit receptor (c-KitR) and tryptase (an agonist of the proteinase-activated receptor-2) take pivotal part in tumor angiogenesis after the MCs activation, contributing to tumor cells invasion and metastasis. In this review, we focused on crucial MCs density (MCD) role in colorectal cancer (CRC) development and progression angiogenesis-mediated; then, we will analyze the principal studies that have focused on MCD as possible prognostic factor. Finally, we will consider a possible role of MCD as novel therapeutic target mainly by c-KitR tyrosine kinase inhibitors (imatinib, masitinib) and tryptase inhibitors (gabexate and nafamostat mesylate) with the aim to prevent CRC progression.

Keywords: Tryptase; Mast cell density; Proteinase-activated receptor-2; c-Kit receptor; Vascular endothelial growth factor; Angiogenesis; Colorectal cancer; Tumor progression; Tryptase inhibitors; c-Kit receptor tyrosine kinase inhibitors

Core tip: In several malignancies it has been well demonstrated that mast cell (MC), activated c-Kit receptor (c-KitR) and tryptase secreted after MC degranulation play a pivotal role in tumor angiogenesis, helping tumor cell invasion and metastasis. The close relationship between MC density, angiogenesis and tumor progression could suggest a role for MCs as a possible prognostic factor in colorectal cancer (CRC). Moreover, considering MC-mediated CRC development, c-KitR tyrosine kinase inhibitors (imatinib, masitinib) and tryptase inhibitors (gabexate and nafamostat mesylate) could be used to block MC activation/degranulation and the tryptase/proteinase-activated receptor-2 axis respectively, and may be evaluated in future clinical trials in CRC patients.